Cytokeratin expression in breast cancer: from mechanisms, progression, diagnosis, and prognosis to therapeutic implications.

Background and aim: Cytokeratins (CKs) are structural proteins vital to epithelial integrity and play key roles in breast cancer progression. This review explores their expression, functions, and therapeutic potential.

Methods: A systematic review was performed using PubMed, Scopus, and Google Scholar. We focused on in vivo, in vitro, and human studies - as well as review articles - published through 1982 that included keywords such as KRT5/13/16/17/18/19/23/80, Cytokeratin 5/13/16/17/18/19/23/80, Keratin 5/13/16/17/18/19/23/80, CK5/13/16/17/18/19/23/80, Cancer, Tumor, Breast cancer, Triple-negative breast cancer, and TNBC. Following title, abstract, and full-text screening of extracted studies, irrelevant articles and duplicates were excluded.

Results: CK5 and CK17 are strongly associated with aggressive breast cancer subtypes, particularly triple-negative breast cancer (TNBC), influencing tumor invasiveness and drug resistance. CK18 and CK19 play key roles in estrogen receptor signaling and epithelial stability. Newly identified CKs, CK23 and CK80, show strong correlations with metastasis and poor prognosis. CK-driven pathways, such as the Wnt/β-catenin and EMT pathways, contribute to tumor progression and therapy resistance.

Conclusion: CKs are key biomarkers for breast cancer classification, prognosis, and therapy response. Their roles in tumor biology suggest potential for targeted treatment and personalized care to improve outcomes.